Compensatory evolution drives multidrug-resistant tuberculosis in central Asia

Matthias Merker*, Maxime Barbier, Helen Cox, Jean Philippe Rasigade, Silke Feuerriegel, Thomas Andreas Kohl, Roland Diel, Sonia Borrell, Sebastien Gagneux, Vladyslav Nikolayevskyy, Sönke Andres, Ulrich Nübel, Philip Supply, Thierry Wirth, Stefan Niemann

*Korrespondierende/r Autor/-in für diese Arbeit
25 Zitate (Scopus)


Bacterial factors favoring the unprecedented multidrug-resistant tuberculosis (MDR-TB) epidemic in the former Soviet Union remain unclear. We utilized whole genome sequencing and Bayesian statistics to analyze the evolutionary history, temporal emergence of resistance and transmission networks of MDR Mycobacterium tuberculosis complex isolates from Karakalpakstan, Uzbekistan (2001–2006). One clade (termed Central Asian outbreak, CAO) dating back to 1974 (95% HPD 1969–1982) subsequently acquired resistance mediating mutations to eight anti-TB drugs. Introduction of standardized WHO-endorsed directly observed treatment, short-course in Karakalpakstan in 1998 likely selected for CAO-strains, comprising 75% of sampled MDR-TB isolates in 2005/2006. CAO-isolates were also identified in a published cohort from Russia (2008– 2010). Similarly, the presence of mutations supposed to compensate bacterial fitness deficits was associated with transmission success and higher drug resistance rates. The genetic make-up of these MDR-strains threatens the success of both empirical and standardized MDR-TB therapies, including the newly WHO-endorsed short MDR-TB regimen in Uzbekistan.

PublikationsstatusVeröffentlicht - 10.2018

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  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)


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